Medical container

ABSTRACT

A medical container produced from a film or sheet having at least one resin layer comprising a polyolefin resin composition, wherein the polyolefin resin composition comprises (A) at least one propylene-base polymer selected from the group consisting of (A1) a specific propylene-base polymer composition, (A2) a propylene-base block copolymer and (A3) a specific propylene-base block copolymer composition, and (B) an ethylene-base copolymer comprising an ethylene and at least one α-olefin having 4 or more carbon atoms, and the refractive index of the xylene-soluble portion is from 1.480 to 1.495.

The present invention relates to a medical container, which is used byfilling blood, medicament or the like in it. The application claims thebenefit of U.S. provisional Application No. 60/455,564, filed on Mar.19, 2003, which is hereby incorporated by reference, and is based onJapanese Patent Application No. 2003-033440 filed on Feb. 12, 2003,which is hereby incorporated by reference.

TECHNICAL FIELD BACKGROUND ART

A medical container for filling blood, medicament or the like isdemanded not only to be, needless to say, hygienic but also to have highheat resistance capable of enduring sterilization treatment at a hightemperature, transparency to enable the check of mingling of a foreignmaterial or visual inspection of the change by blending of a medicament,impact resistance sufficiently high to prevent the bag from rupturing atfalling on handling or at packaging and transportation, flexibility forfacilitating the discharge of contents, and blocking resistance not toreadily cause separation of film or sheet at the production of a medicalcontainer or not to contact a medicament-containing medical containerwith its outer packaging bag.

In particular, demands are increasing for a medical container which canbe sterilized at a high temperature of 121° C. or more having a strongsterilization power, can satisfy all of heat resistance, transparency,impact resistance, flexibility and blocking resistance, and can beindustrially produced.

For the medical container, a soft polyvinyl chloride, apolyethylene-base material such as high-pressure low-densitypolyethylene, linear low-density polyethylene, high-density polyethyleneand ethylene-vinyl acetate copolymer, and a polypropylene-base materialsuch as propylene homopolymer and random or block copolymer of propyleneand other α-olefin have been heretofore used.

The vinyl chloride-base resin is excellent in the balance of heatresistance, transparency, flexibility and impact resistance but thisresin has a problem in that a plasticizer used for imparting theperformance dissolves out into a medicament solution or food.

Out of polyethylene-base materials, the high-pressure low-densitypolyethylene is deficient in that the heat resistance or impact strengthis poor. As for the linear low-density polyethylene, a polyethylenehaving a low density is used so as to enhance the transparency orflexibility, but when the density is decreased, insufficient heatresistance is liable to result and furthermore, problems arise, forexample, the low molecular weight component of the resin lowers theblocking resistance of the container or dissolves out into a medicament.The ethylene-vinyl acetate copolymer is excellent in the transparencybut disadvantageously low in the heat resistance. The high-densitypolyethylene is deficient in that the transparency and impact resistanceare poor. Thus, polyethylene-base materials cannot satisfy a goodbalance of heat resistance, transparency and impact resistance.

Out of polypropylene-base materials, the propylene homopolymer andpropylene random copolymer are excellent in the transparency butinferior in the blocking resistance, and the propylene block copolymeris poor in the balance of flexibility, impact resistance andtransparency.

For solving these problems, with respect to the medical container usinga polyethylene-base material, a multilayer container having a layermainly comprising a high-density polyethylene and a layer mainlycomprising a linear low-density polyethylene has been proposed (see, forexample, JP-A-5-293160 (the term “JP-A” as used herein means an“unexamined published Japanese patent application”).

Furthermore, a polyethylene-base material produced by using ametallocene-base catalyst and having excellent impact resistance andtransparency has been recently developed and studies are being made toapply this material to a medical container. Also, a method of usingthese materials in combination and stacking two, three or more layershas been proposed (see, for example, JP-A-7-125738).

On the other hand, with respect to the medical container using apolypropylene-base material, a technique of using a resin compositioncomprising a propylene-base random copolymer having an α-olefin contentof 5 to 8 mass % and a mixture of specific ethylene-propylene andethylene-butene random copolymers to obtain a container excellent in theheat resistance, transparency, impact resistance and the like has beendisclosed (see, for example, JP-A-8-231787).

Also, a container having a constitution such that a layer comprising apropylene homopolymer or propylene-α-olefin random copolymer containingfrom 0 to 30% of a polyethylene-base resin is provided as the outerlayer and a three-layer laminate comprising a mixture of a propylenehomopolymer or a propylene/α-olefin random copolymer and an olefin-baseelastomer or the like is provided as the intermediate layer has beenproposed (see, for example, JP-A-9-262948).

Furthermore, a technique of using a resin composition comprising acrystalline polypropylene and a propylene/α-olefin copolymer having aspecific limiting viscosity ratio, and forming a specific morphology atthe thermoformation has been proposed (see, for example,JP-A-10-316810).

However, the container described in JP-A-5-293160 cannot always hold asufficient transparency after sterilization at a temperature of 121° C.or more and fails in fully satisfying the requirement on the market thatsterilization can be performed at a higher temperature in a shortertime.

Also in the case of using the laminate described in JP-A-7-125738, thetransparency after high-temperature sterilization of 121° C. or more isnot sufficiently high and moreover, the impact resistance is alsoinsufficient to readily cause rupture at the heat-welded part on fallingof the container, therefore, improvements are demanded. Furthermore, afilm or sheet obtained by a water cooling inflation method, a T-diemethod or the like has particularly a smooth surface and readily causesblocking of films or sheets with each other and when these are pulledapart, a whitened flaw remains on the surface and the outer appearanceis seriously deteriorated in some cases.

The resin composition described in JP-A-8-231787 has a problem that theheat resistance and transparency are still insufficient.

The container described in JP-A-9-262948 does not have a sufficientlyhigh impact resistance and particularly, in the case of a containerhaving a volume of 1 L or more, the impact resistance is not satisfiedfrom the standpoint of preventing rupture on falling.

The method described in JP-A-10-316810 has a problem in that not onlythe impact resistance or the thermal shrinkage percentage at the heatsterilization expresses strong anisotropy due to orientation of thedomain but also stable production while keeping the quality can behardly attained because the formation of specific morphology issensitive to the molding conditions or the like.

The present invention has been made under these circumstances and anobject of the present invention is to provide a medical container havingheat resistance high enough to enable sterilization at a temperature of121° C. or more and exhibiting excellent properties in all of thetransparency, impact resistance, flexibility and blocking resistance.

DISCLOSURE OF INVENTION

As a result of extensive investigations, the present inventors havefound that the above-described object can be attained by a medicalcontainer using a polyolefin resin composition containing specificcomponents, where the xylene-soluble portion has a refractive indexwithin a specific range. Based on this finding, the following medicalcontainer has been accomplished.

More specifically, the medical container of the present invention isproduced from a film or sheet having at least one resin layer comprisinga polyolefin resin composition, wherein the polyolefin resin compositioncomprises (A) at least one propylene-base polymer selected from thegroup consisting of (A1) a propylene-base polymer composition as amixture of (A11) a propylene polymer and (A12) an ethylene-propylenecopolymer elastomer, (A2) a propylene-base block copolymer, and (A3) apropylene-base block copolymer composition as a mixture of (A2) apropylene-base block copolymer and (A12) an ethylene-propylene copolymerelastomer, and (B) an ethylene-base copolymer comprising an ethylene andat least one α-olefin having 4 or more carbon atoms, and the refractiveindex of the xylene-soluble portion is from 1.480 to 1.495.

In the medical container of the present invention, the polyolefin resincomposition preferably has a xylene-soluble portion content of 20 to 70mass %.

Furthermore, in the polyolefin resin composition, the ratio(MFR_(A)/MFR_(B)) of the melt flow rate (MFR_(A)) of the propylene-basepolymer (A) to the melt flow rate (MFR_(B)) of the ethylene-basecopolymer (B) is preferably from 0.3 to 3.0.

The medical container of the present invention may also be produced suchthat the film or sheet has a first high-density polyethylene layercontaining a high-density polyethylene and this first high-densitypolyethylene layer is disposed in the inner side.

The medical container of the present invention may also be produced suchthat the film or sheet has a second high-density polyethylene layercontaining a high-density polyethylene and this second high-densitypolyethylene layer is disposed in the outer side.

In the case where the film or sheet has a first high-densitypolyethylene layer, the first high-density polyethylene layer preferablycontains 20 mass % or more of a high-density polyethylene having adensity of 0.950 g/cm³ or more.

In the case where the film or sheet has a second high-densitypolyethylene layer, the second high-density polyethylene layerpreferably contains 20 mass % or more of a high-density polyethylenehaving a density of 0.950 g/cm³ or more.

In the medical container of the present invention, the thickness of theresin layer comprising a polyolefin resin composition preferablyoccupies 60% or more of the entire thickness of the film or sheet.

In the present specification, unless otherwise indicated, MFR is a valuemeasured at 230° C. with a load of 21.18 N according to JIS K 7210.

The medical container of the present invention is presumed to haveexcellent properties because of the following reasons. That is, a resincomponent having high crystallinity is considered to impart heatresistance to the resin and a rubber-analogous resin component havinglow crystallinity is considered to impart the impact resistance.Usually, the refractive index greatly differs between a component havinghigh crystallinity and a component having low crystallinity andtherefore, a mixture of these components is decreased in thetransparency. However, in the polyolefin resin composition for use inthe medical container of the present invention, the component having lowcrystallinity has a specific refractive index. More specifically, therefractive index of the xylene-soluble portion presumed to contain a lowcrystallinity component is in a specific range and the difference in therefractive index between the low crystallinity component and the highcrystallinity component is considered to become small, so that heatresistance and impact resistance can be imparted without decreasing thetransparency. By using a film or sheet having at least one layercomprising this polyolefin resin composition, a medical containerexcellent in the transparency, impact resistance, heat resistance,flexibility and blocking resistance can be obtained.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention is described in detail below.

The medical container of the present invention is produced from a filmor sheet having at least one resin layer comprising a polyolefin resincomposition and has, for example, a bag form.

The polyolefin composition contains (A) a propylene-base polymer and (B)an ethylene-base copolymer and the xylene-soluble portion thereof has arefractive index of 1.480 to 1.495.

The propylene-base polymer (A) is at least one member selected from thegroup consisting of (A1) a propylene-base polymer composition as amixture of (A11) a propylene polymer and (A12) an ethylene-propylenecopolymer elastomer, (A2) a propylene-base block copolymer, and (A3) apropylene-base block copolymer composition as a mixture of (A2) apropylene-base block copolymer and (A12) an ethylene-propylene copolymerelastomer.

The propylene polymer (A11) (hereinafter, sometimes simply referred toas a component (A11)) contained in the propylene-base polymercomposition (A1) is a propylene homopolymer or a propylene-ethylenerandom polymer comprising propylene and ethylene and having an ethylenecontent of 5 mass % or less.

The melt flow rate (hereinafter referred to as “MFR”) of the propylenepolymer (A11) is not particularly limited but this is preferably from0.1 to 50 g/10 min, more preferably from 0.5 to 20 g/10 min, still morepreferably from 0.5 to 5 g/10 min, because the mold processability, heatresistance and impact resistance all can be enhanced.

The ethylene-propylene copolymer elastomer (A12) (hereinafter, sometimessimply referred to as a component (A12)) contained in the propylene-basepolymer composition (A1) is a copolymer elastomer substantiallycomprising only ethylene and propylene and having a propylene-originatedunit content of 50 to 85 mass %. The MFR of the ethylene-propylenecopolymer elastomer (A12) is not particularly limited but this ispreferably from 0.1 to 50 g/10 min, more preferably from 0.5 to 20 g/10min, still more preferably from 0.5 to 5 g/10 min, because the moldprocessability, heat resistance and impact resistance all can beenhanced.

The proportion of the propylene polymer (A11) occupying in thepropylene-base polymer composition (A1) is, in view of high heatresistance, preferably from 90 to 30 mass %, more preferably from 85 to50 mass %, still more preferably from 80 to 65 mass %, per 100 mass % intotal of components (A11) and (A12).

The propylene-base block copolymer (A2) (hereinafter, sometimes simplyreferred to as a component (A2)) is a propylene-ethylene block copolymerobtained by melt-kneading a polymer material mixture produced through afirst step of polymerizing a propylene homopolymer or a propylene andethylene copolymer having an ethylene content of less than 5 mass % andsubsequently a second step of polymerizing a propylene and ethylenecopolymer having an ethylene content of 10 to 70 mass % in apolymerization vessel consisting of at least two vessels, which may bethe same as or different from that used in the polymerization of thefirst step.

In the propylene-base block copolymer (A2), the proportion of thepolymer produced in the first step is not particularly limited but thisis preferably from 90 to 30 mass % and in view of profitability in theproduction, more preferably from 85 to 50 mass %, still more preferablyfrom 80 to 65 mass %.

The ethylene content of the polymer obtained in the first step isusually less than 5 mass %, preferably less than 4 mass %, morepreferably less than 1.5 mass %. If the ethylene content of the polymerobtained in the first step is 5 mass % or more, the heat resistance atsterilization is liable to decrease.

The ethylene content of the polymer obtained in the second step isusually from 10 to 70 mass %, preferably from 20 to 60 mass %. If theethylene content of the polymer obtained in the second step is less than10 mass %, the impact resistance readily decreases, whereas if itexceeds 70 mass %, the transparency sometimes decreases.

The catalyst used in the polymerization of the first and second steps isnot particularly limited and, for example, a Ziegler.Natta catalyst or ametallocene catalyst is suitably used. The process for thepolymerization may be any of a bulk method, a solution method, a slurrymethod, a vapor phase method and a combination thereof.

The propylene-base block copolymer composition (A3) (hereinafter,sometimes simply referred to as a component (A3)) is a mixture of theabove-described propylene-base block copolymer (A2) and anethylene-propylene copolymer elastomer (A12). The mixing ratio of (A2)and (A12) is, in view of high heat resistance, preferably from 90:10 to50:50, more preferably from 80:20 to 50:50.

Among those components (A1), (A2) and (A3), the propylene-base polymer(A) is preferably the component (A2), namely, a propylene-base blockcopolymer, because this component expresses stable performance and isinexpensive.

The MFR of the propylene-base polymer (A) is not particularly limitedbut this is preferably from 0.1 to 50 g/10 min, more preferably from 0.5to 20 g/10 min, still more preferably from 0.5 to 5 g/10 min, becausethe mold processability, heat resistance and impact resistance all canbe enhanced.

The ethylene-base copolymer (B) (hereinafter, sometimes simply referredto as a component (B)) is a copolymer consisting of an ethylene and atleast one α-olefin having 4 or more carbon atoms and mainly comprisingan ethylene-originated unit (50 mass % or more). Examples of theα-olefin include 1-butene, 1-pentene, 4-methyl-1-pentene, 1-hexene and1-octene. As the ethylene-base copolymer (B), one or more of thesecopolymers is(are) used.

The density (according to JIS K 7112 Method D) of the ethylene-basecopolymer (B) is usually 0.915 g/cm³ or less and in view of hightransparency, preferably less than 0.905 g/cm³, more preferably lessthan 0.900 g/cm³.

The MFR of the ethylene-base copolymer (B) is not particularly limitedbut this is preferably from 0.1 to 20 g/10 min, because the moldprocessability, heat resistance and impact resistance all can beenhanced.

In the polyolefin resin composition containing these components (A) and(B), the refractive index of the xylene-soluble portion which dissolvesin xylene at ordinary temperature is from 1.480 to 1.495, preferablyfrom 1.480 to 1.490. When the refractive index of the xylene-solubleportion falls in this range, both the impact resistance and thetransparency can be satisfactorily high. If the refractive index of thexylene-soluble portion is less than 1.480 or exceeds 1.495, thetransparency decreases.

The refractive index of the xylene-soluble portion becomes higher as thedensity of the ethylene-base copolymer (B) increases, and becomes loweras the density of the ethylene-base copolymer (B) decreases.

The proportion and refractive index of the xylene-soluble portion aredetermined as follows.

A specimen (10 g) of a polyolefin resin composition is added to 1 L ofan orthoxylene and after the temperature is elevated to a boilingtemperature (about 135° C.) by stirring the solution under heating, thespecimen is completely dissolved over 30 minutes or more. Afterconfirming the complete dissolution with an eye, the solution is leftstanding with stirring to cool to 100° C. or less and held in aconstant-temperature bath kept at 25° C. for 2 hours. Thereafter, theprecipitated component (xylene-insoluble portion Xi) is separated byfiltration through a filter paper to obtain a filtrate. The obtainedfiltrate is heated at a temperature of 140° C. to distill out xylene ina nitrogen stream (about 1 L/min) and the residue is dried to obtain axylene-soluble portion Xs. At this time, the drying of xylene-insolubleportion and xylene-soluble portion is performed at 60° C. under reducedpressure for one day.

The proportion of the xylene-soluble portion is determined by (mass ofXs/mass of specimen).

The xylene-soluble portion is composed of a low molecular material inthe polyolefin resin composition, a non-crystalline molecule, and thelike.

In the measurement of refractive index of the xylene-soluble portion,the xylene-soluble portion is preheated at 230° C. for 5 minutes in apress-molding machine, then degassed for 30 seconds, pressed at 6 MPafor 1 minute and cooled at 30° C. for 3 minutes to obtain a film havinga thickness of 50 to 80 μm. Subsequently, a specimen comprising thisfilm is left standing at ordinary temperature for 24 hours and thenmeasured on the refractive index for sodium D line at 23° C. by an Abberefractive index meter (manufactured by Atago Co. Ltd.) using ethylsalicylate as the intermediate solution.

The content of the xylene-soluble portion in the polyolefin resincomposition is preferably from 10 to 70 mass %, more preferably from 20to 70 mass %. If the xylene-soluble portion content is less than 10 mass%, the impact strength at low temperatures is liable to be insufficient,whereas if it exceeds 70 mass %, the heat resistance is sometimes notsatisfied.

In the polyolefin resin composition, the ratio (MFR_(A)/MFR_(B)) of theMFR (MFR_(A)) of the propylene-base polymer (A) to the MFR (MFR_(B)) ofthe ethylene-base copolymer (B) is preferably from 0.3 to 3.0, morepreferably from 0.3 to 2.5, still more preferably from 0.3 to 2.0. Ifthe MFR ratio is less than 0.3, the impact resistance at lowtemperatures is liable to be insufficient, whereas if it exceeds 3.0,fish eye is readily generated on the film to impair the outerappearance.

The proportion of the component (A) in the polyolefin resin compositionis not particularly limited as long as the refractive index of thexylene-soluble portion is in the range from 1.480 to 1.495, but in viewof higher heat resistance, this is usually on the order of 40 to 90 mass%, preferably from 50 to 70 mass %.

In the polyolefin resin composition, another polymer may be blendedwithin the range of not impairing the object of the present invention.Specific examples of the another polymer which can be blended in thepolyolefin resin composition include polyethylene-base resins such ashigh-pressure low-density polyethylene, linear low-density polyethyleneand high-density polyethylene, various styrene-base elastomer such asstyrene-butadiene elastomer and hydrogenated product thereof, randomcopolymers of propylene and an α-olefin having 4 or more carbon atoms,an ethylene-vinyl acetate copolymer, copolymers of ethylene and a(meth)acrylic acid (ester), and olefin-base thermo-plastic elastomers.The proportion of this another polymer contained is preferably less than40 mass % per 100 mass % of the polyolefin resin composition.

Examples of the method for producing the polyolefin resin compositioninclude a melt-kneading method. In the case of melt-kneading thecomponents (A1), (A2) and (B), for example, the component (A2) may bemelt-mixed after melt-mixing the components (A11), (A12) and (B). Atthis time, the order of melt-mixing the components (A11), (A12) and (B)is not particularly limited and the component (B) may be melt-kneadedafter obtaining the component (A1) by melt-kneading the components (A11)and (A12), or the components (A11), (A12) and (B) may be simultaneouslymelt-kneaded. For the melt-kneading, a single-screw or twin-screwextruder can be usually used.

The thus-produced polyolefin resin composition contains (A) apropylene-base polymer and (B) an ethylene-base copolymer and thexylene-soluble portion in the polyolefin-base resin composition, whichis presumed to be a low crystalline component, has a refractive index of1.480 to 1.495, so that the resin composition can be excellent not onlyin the heat resistance but also in all of the transparency, impactresistance, flexibility and blocking resistance.

The film or sheet constituting the medical container has at least oneresin layer comprising the above-described polyolefin resin composition.Such a film or sheet is formed by, for example, an air-cooling orwater-cooling inflation molding method or a T-die method.

This film or sheet may be a single-layer film or sheet composed of aresin layer comprising the polyolefin resin composition or may be amultilayer film or sheet including a resin layer comprising thepolyolefin resin composition.

The thickness of the film or sheet is usually from 30 to 1,000 μm and inview of flexibility and strength, preferably from 50 to 700 μm, morepreferably from 100 to 500 μm.

In the case where the film or sheet is composed of two or more layers,by taking account of transparency, impact resistance and heatresistance, the thickness of the resin layer comprising the polyolefinresin composition preferably occupies 60% or more of the entirethickness of the film or sheet.

In the case of a multilayer film or sheet, the multilayer film can beproduced by an extrusion lamination method of laminating a single layeror multilayer melt resin including at least one resin layer comprisingthe above-described polyolefin resin composition on a film formed of thesame or different material, or by a dry lamination method of laminatinga film formed of the same or different material and a single layer ormultilayer body including at least one resin layer comprising theabove-described polyolefin resin composition, through an adhesive.

The medical container is produced from a film or a sheet and has, forexample, a bag form. This medical container may be a single chambercontainer or a container with multiple chambers divided by an easilyseparable partition part or a resin-made partition member. If desired,the medical container may be fixed with a mouth member for injection orejection or with another medicament container for the purpose of mixedinfusion, by heat-sealing or the like.

Examples of the method for producing the medical container include amethod of cutting the above-described film or sheet and heat-sealing themarginal parts thereof to form a desired container shape. In thismethod, the order of cutting and heat-sealing may be reversed.

The heat-sealing method at the formation of the film or sheet into acontainer shape is not particularly limited and, for example, weldingmethods such as hot-plate sealing method, high-frequency sealing methodand ultrasonic wave sealing method can be employed. However, theheat-sealing conditions such as heat-sealing temperature and shape ofthe heat-sealed part are preferably set not to impair the performance ofthe medical container, such as outer appearance and impact resistance.

The medical container can be easily produced when it is formed of asingle layer film or sheet, and is more enhanced in the hygiene, heatresistance and the like when it is formed of a multilayer film or sheet.

Particularly, when the film or sheet is a multilayer body having a firsthigh-density polyethylene layer containing a high-density polyethyleneand the medical container is produced by disposing the firsthigh-density polyethylene layer in the inner side, a medicament comesinto contact with this first high-density polyethylene layer andtherefore, not only the hygiene is more improved but also the impactresistance at low temperatures, the appearance of heat-sealed part, thestrength and the like are enhanced.

Also, when the film or sheet is a multilayer body having a secondhigh-density polyethylene layer containing a high-density polyethyleneand the medical container is produced by disposing this secondhigh-density polyethylene layer in the outer side, the impact resistanceat low temperatures is enhanced. In particular, a medical containerproduced by disposing the second high-density polyethylene layer as theoutermost layer is preferred, because blocking with the outer packagingmaterial of the medical container hardly occurs.

Accordingly, in a more preferred embodiment, the medical container has ahigh-density polyethylene layer in the inner and outer sides.

Furthermore, when the film or sheet is a multilayer body having a layercontaining a propylene-ethylene random copolymer and the medicalcontainer is produced by disposing this propylene-ethylene randomcopolymer-containing layer in the inner side and/or in the outer side,the heat resistance is more enhanced.

The high-density polyethylene contained in the first high-densitypolyethylene layer and the second high-density polyethylene layer is anethylene homopolymer or an ethylene • α-olefin copolymer of ethylene anda slight amount of α-olefin having from 3 to 12 carbon atoms. Examplesof the α-olefin in the ethylene.α-olefin copolymer include propylene,1-butene, 1-pentene, 1-hexene, 4-methyl-1-pentene, 1-octene, 1-deceneand 1-dodecene. These are used individually or in combination of two ormore. Among these, 1-butene, 1-pentene, 1-hexene, 4-methyl-1-pentene and1-octene are preferred.

Such a high-density polyethylene is produced by various processes suchas slurry method, vapor phase method and solution method, preferablyusing a Ziegler.Natta catalyst or a metallocene catalyst.

The density (according to JIS K 7112. Method D) of this high-densitypolyethylene is usually 0.940 g/cm³ or more, preferably 0.950 g/cm³ ormore, more preferably 0.955 g/cm³ or more. If the density is less than0.940 g/cm³, insufficient heat resistance results in some cases anddeformation, shrinkage or reduction of transparency may occur at thesterilization at a temperature exceeding 121° C.

The MFR (at 190° C. with a load of 21.18 N according to JIS K 7210) ofthe high-density polyethylene is approximately from 0.1 to 50 g/10 min,preferably from 0.5 to 20 g/10 min. With an MFR of approximately from0.1 to 50 g/10 min, an appropriate melt tension can be obtained at themolding and a film or sheet can be easily formed.

In the first and second high-density polyethylene layers, anotherpolymer may be blended within the range of not impairing the objet ofthe present invention. Specific examples of the another polymer includepolyethylene resins such as high-pressure low-density polyethylene andlinear low-density polyethylene, polypropylene resins such as propylenehomopolymer, propylene.α-olefin random copolymer and propylene.α-olefinblock copolymer, various styrene-base elastomers such asstyrene-butadiene elastomer, ethylene.propylene elastomer, anethylene-vinyl acetate copolymer, copolymers of ethylene and(meth)acrylic acid (ester), and olefin-base thermoplastic elastomers.The another polymer is blended for the purpose of, for example,adjusting the peel strength at the marginal part of a medical containeror at the easily separable partition part of a multiple chambercontainer.

In the case of blending another polymer, the high-density polyethylenehaving a density of 0.950 g/cm³ or more is preferably contained in anamount of usually 20 mass % or more, preferably 30 mass % or more, morepreferably 70 mass % or more, still more preferably 90 mass % or more ineach of the first and second high-density polyethylene layers. As longas the high-density polyethylene having a density of 0.950 g/cm³ or moreis contained in an amount of 20 mass % or more, heat sterilization at121° C. or more can be performed even when the first or secondhigh-density polyethylene layer is provided, and moreover, the blockingresistance of film is more enhanced.

The preferred thickness of each of the first and second high-densitypolyethylene layers varies depending on the high-density polyethylenecontent but when the high-density polyethylene is contained in an amountof 90 mass % or more, the thickness is preferably from 5 to 40 μm.

The finally obtained medical container is used by filling a medicamentand then subjecting it to steam sterilization under high pressure. Thesteam sterilization temperature is not particularly limited but this isgenerally from 100 to 140° C. Other known sterilization methods such asultraviolet ray and electron beam can also be used in combination withthe high-temperature high-pressure heat sterilization.

The thus-obtained medical container is produced from a film or sheetcomprising the above-described polyolefin-base resin composition andtherefore, exhibits excellent property not only in the heat resistancebut also in all of the transparency, impact resistance, flexibility andblocking resistance. In particular, even when sterilized at 121° C. ormore having a high sterilization effect, excellent property is exhibitedin all of the transparency, impact resistance, flexibility and blockingresistance and therefore, this medical container is useful.

In any of the resin materials for use in the medical container, commonlyemployed known additives can be appropriately blended within the rangeof not impairing the effect of the present invention, if desired, suchas antistatic agent, antioxidant, lubricant, anti-blocking agent,anti-clouding agent, nuclear agent, organic and inorganic pigments,ultraviolet absorbent, dispersing agent and reinforcing agent (e.g.,talc, calcium carbonate) However, the blending amount thereof must bewithin the range admitted in the medical field and in particular, theseadditives are preferably not blended in a layer which comes into directcontact with the contents.

EXAMPLES

The present invention is described in greater detail below by referringto Examples, however, the present invention is not limited to theseExamples. In the following description, unless otherwise indicated, thepercentage “%” is on a mass basis.

Examples 1 to 9 and Comparative Examples 1 to 5

<Resin Material>

The resins used in Examples and Comparative Examples are as follows.

[Propylene Polymer (A11)]

A11-1:

Propylene homopolymer (PL300A produced by SunAllomer Ltd.); MFR: 1.7g/10 min, xylene-soluble content: 0.5%.

A11-2:

Propylene-ethylene random copolymer having, an ethylene content of 3mass % (PB222A produced by SunAllomer Ltd.); MFR: 0.8 g/10 min,xylene-soluble content: 3.1%.

[Ethylene-Propylene Copolymer Elastomer (A12)]

A12-1:

Ethylene-propylene copolymer (Tafmer P0680 produced by Mitsui Chemicals,Inc.); MFR: 0.7 g/10 min, density: 0.885 g/cm³.

[Propylene-Base Block Copolymer (A2)]

A2-1:

Propylene-ethylene block copolymer obtained through a first-steppolymerization and a second-step polymerization, which is apropylene-ethylene block copolymer containing 75% of a propylenehomopolymer obtained in the first step and 25% of a propylene-ethylenecopolymer having an ethylene content of 35% obtained in the second step;MFR: 1.0 g/10 min, xylene-soluble content: 26%. This copolymer A2-1 wasproduced as follows.

(1) Preparation of Solid Catalyst

In a nitrogen atmosphere, 56.8 g anhydrous magnesium chloride wascompletely dissolved at 120° C. in 100 g of absolute ethanol, 500 mL ofpetrolatum oil “CP15N” produced by Idemitsu Kosan Co., Ltd. and 500 mLof silicone oil “KF96” produced by Shin-Etsu Silicone Co., Ltd. Theresulting solution was stirred at 120° C. and 5,000 revolutions/min for2 minutes by using TK Homomixer manufactured by Tokushu Kika Kogyo Co.,Ltd. While continuing the stirring, the solution was transferred to 2liter of anhydrous heptane by taking care not to exceed 0° C., therebyprecipitating a white solid. The white solid obtained was thoroughlywashed with anhydrous heptane, vacuum-dried at room temperature and thenpartially deprived of ethanol in nitrogen stream. Subsequently, 30 g ofMgCl₂.1.2C₂H₅OH obtained as a spherical solid was suspended in 200 mL ofanhydrous heptane and thereto, 500 mL of titanium tetrachloride wasadded dropwise over 1 hour with stirring at 0° C. Thereafter, thesuspension was heated and when reached 40° C., 4.96 g of diisobutylphthalate was added. Then, the temperature was elevated to 100° C. overabout 1 hour. After the reaction at 100° C. for 2 hours, the solidportion was sampled by hot filtration, 500 mL of titanium tetrachloridewas added to this reaction product, and the resulting mixture wasstirred and then reacted at 120° C. for 1 hour. After the completion ofreaction, the solid portion was again removed by hot filtration andwashed 7 times with 1.0 liter of hexane at 60° C. and then 3 timeswith 1. 0 liter of hexane at room temperature to obtain a solidcatalyst. The titanium content in the solid catalyst component obtainedwas measured and found to be 2.36 mass %.

(2) Prepolymerization

Into a 3-liter autoclave, 500 mL of n-heptane, 6.0 g oftriethylaluminum, 0.99 g of cyclohexylmethyldimethoxy-silane and 10 g ofpolymerization catalyst obtained above were charged in a nitrogenatmosphere and stirred at a temperature of 0 to 5° C. for 5 minutes.Subsequently, propylene was supplied to the autoclave such that 10 g ofpropylene was polymerized per 1 g of the polymerization catalyst, andprepolymerization was performed at a temperature of 0 to 5° C. for 1hour. The prepolymerization catalyst obtained was washed 3 times with500 mL of n-heptane and then used in the following main polymerization.

(3) Main Polymerization

(First Step: Production of Propylene Homopolymer)

Into an autoclave equipped with a stirrer and having an inner volume of60 liter, 2.0 g of a prepolymerization solid catalyst prepared as above,11. 4 g of triethylaluminum and 1.88 g ofcyclohexylmethyldimethoxysilane were charged in a nitrogen atmosphere.Thereto, 18 kg of propylene and hydrogen in an amount of 5,000 mol ppmbased on the propylene were charged and after elevating the temperatureto 70° C., the polymerization was performed for 1 hour. After 1 hour,unreacted propylene was removed to complete the polymerization.

(Second Step: Production of Propylene-Ethylene Copolymer)

After the completion of first-step polymerization, liquid propylene wasremoved and subsequently, hydrogen and an ethylene/propylene (26/74 (bymass)) mixed gas of 2.2 Nm³/hour were supplied at 75° C. to have ahydrogen concentration of 40,000 mol ppm based on the total amount ofethylene, propylene and hydrogen, and then the polymerization wasperformed for 60 minutes. Thereafter, unteacted gas was removed tocomplete the polymerization. As a result, 6.6 kg of a polymer materialmixture was obtained.

To 100 parts by mass of the polymer material mixture obtained above,0.30 parts by mass of phenol-base antioxidant and 0.1 part by mass ofcalcium stearate were added and mixed by a Henschel mixer at roomtemperature for 3 minutes. The resulting mixture was melt-kneaded by anextruder having a screw aperture of 40 mm (Nakatani Model VSK 40-mmExtruder) at a cylinder temperature set to 210° C. to obtainpropylene-ethylene block copolymer (A2-1) pellets.

A2-2:

Propylene-ethylene block copolymer obtained through a first-steppolymerization and a second-step polymerization, which is apropylene-ethylene block copolymer containing 80% of apropylene-ethylene random copolymer having an ethylene content of 2%obtained in the first step and 20% of a propylene-ethylene copolymerhaving an ethylene content of 50% obtained in the second step; MFR: 1.0g/10 min, xylene-soluble content: 26%. This copolymer A2-2 was producedas follows.

(First Step: Production of Propylene-Ethylene Random Copolymer)

Into an autoclave equipped with a stirrer and having an inner volume of60 liter, 2.0 g of a prepolymerization solid catalyst prepared in thesame manner as in Production of A2-1, 11.4 g of triethylaluminum and1.88 g of cyclohexylmethyldimethoxysilane were charged in a nitrogenatmosphere. Thereto, 18 kg of propylene, 120 L of ethylene and hydrogenin an amount of 6,500 mol ppm based on the propylene were charged andafter elevating the temperature to 70° C., the polymerization wasperformed for 1 hour. After 1 hour, unreacted propylene was removed.

(Second Step: Production of Propylene-Ethylene Copolymer)

The polymerization was performed in the same manner as in Production ofA2-1 except that an ethylene/propylene mixed gas at a mass ratio of44/56 and hydrogen in an amount of giving a concentration of 40,000 molppm were supplied and after performing the polymerization for 40minutes, unreacted gas was removed to complete the polymerization. Bythis production method, 5.7 kg of a polymer material mixture wasobtained.

From this polymer material mixture, propylene-ethylene block copolymer(A2-2) pellets were obtained in the same manner as in Production ofA2-1.

[Ethylene-Base Copolymer (B)]

B-1:

Ethylene-1-butene copolymer (EBM2021P produced by JSR); MFR: 2.6 g/10min, density: 0.88 g/cm³.

B-2:

Ethylene-1-butene copolymer (Tafmer A4085 produced by Mitsui Chemicals,Inc.); MFR: 6.7 g/10 min, density: 0.88 g/cm³.

B-3:

Ethylene-1-butene copolymer (EBM3021P produced by JSR); MFR: 2.6 g/10min, density: 0.86 g/cm³.

B-4:

Ethylene-1-butene copolymer (Engage 8480 produced by DuPont DowElastomers Japan K.K.), MFR: 2 g/10 min, density: 0.902 g/cm³.

[Other Component]

PE1:

High-density polyethylene, density: 0.955 g/cm³, MFR: 3.0 g/10 min.

PE2:

Linear low-density polyethylene, density: 0.905 g/cm³, MFR: 1.0 g/10min.

<Measurement of Physical Properties of Resin Material>

MFR:

MFR of each component of propylene-base polymer (A) and MFR ofethylene-base copolymer (B) were measured at 230° C. with a load of21.18 N according to JIS K 7210. MFR of high-density polyethylene andlinear low-density polyethylene was measured at 190° C. with a load of21.18 N according to JIS K 7210.

Density:

This was measured according to JIS K 7112 Method D.

Xylene-soluble content:

This was measured by the method described in Mode for Carrying Out theInvention.

Refractive Index:

This was measured by the method described in Mode for Carrying Out theInvention.

<Production of Polyolefin Resin Composition>

The resin materials described above were blended at the compositionalratio shown in Table 1, mixed by Henschel mixer for 3 minutes and thenmelt-kneaded at temperature of 230° C. by using a single screw extruderto obtain pellets of polyolefin resin composition. The physicalproperties of this polyolefin resin composition are shown in Table 2.

<Production of Film>

The polyolefin resin composition pellets obtained above were molded intoa tubular film having an entire thickness of 250 μm by a water coolinginflation three-layer molding machine at a temperature of 230° C.Incidentally, in the case where the tubular film was a two-layer film,the inner layer was formed to a thickness of 20 μm, and in the case of athree-layer film, the inner layer and the outer layer both were formedto a thickness of 20 μm.

Separately, a single layer film was molded to have a thickness of 250 μmby a water cooling inflation molding machine. TABLE 1 Propylene-BasePolymer (A) Ethylene- Propylene Propylene-Base Propylene Copolymer BlockCopolymer Polymer (All) Elastomer (A12) (A2) Ethylene-Base Polymer (B)Composition Proportion Proportion Proportion MFR MFR Proportion No.Resin (mass %) Resin (mass %) Resin (mass %) (g/10 min) Resin (g/10 min)(mass %) Composition 1 A11-1 49 A12-1 21 0.9 B-1 2.6 30 Composition 2A2-1 80 1 B-1 2.6 20 Composition 3 A2-1 70 1 B-1 2.6 30 Composition 4A2-1 95 1 B-3 2.6 5 Composition 5 A2-1 45 1 B-4 2.0 55 Composition 6A11-1 90 A12-1 5 1 B-1 2.6 5 Composition 7 A2-1 60 1 B-2 6.7 40Composition 8 A2-1 60 3 B-3 1.8 40 Composition 9 A11-1 60 A12-1 40 0.9

TABLE 2 Xylene-Soluble Portion (Xs) Composition Refractive ProportionNo. Index (mass %) MFR Ratio¹⁾ Composition 1 1.485 48 0.34 Composition 21.482 42 0.38 Composition 3 1.484 49 0.38 Composition 4 1.475 31 0.38Composition 5 1.496 68 0.5 Composition 6 1.485 11 0.38 Composition 71.490 54 0.15 Composition 8 1.481 55 1.67 Composition 9 1.479 21 —¹⁾MFR (at 230° C.) of propylene-base polymer (A)/MFR (at 230° C.) ofethylene-base copolymer (B)<Production of Medical Container and Sample for Measurement>

Tubular films in the state that respective inner surfaces weresuperposed were cut into a length of 20 cm and a width of 20 cm and thenthe length direction and the width direction each was heat-sealed in aseal width of 10 mm. In the inside thereof, 500 mL of water was filledto produce a bag-shaped medical container. At this time, the heatsealing was performed by using a hot-plate heat-sealing machine (a heatsealer manufactured by Tester Sangyo Co,. Ltd.) under a pressure of 0.4MPa at a seal temperature or 170° C. for a sealing time of 1 second. Theobtained medical container was subjected to a sterilization treatment at121° C. for 30 minutes and used as a sample for measurement of thefollowing various physical properties. However, the sample for theevaluation of blocking resistance only was subjected to a sterilizationtreatment at 121° C. in the state that respective inner layers werealmost contacted by filling 2 mL of water into the inside and extractingthe inner air by means of a vacuum pump.

<Measurement of Various Physical Properties>

The measurement results of the following various physical properties areshown in Table 3.

[Heat Resistance]

The appearance of the container after sterilization treatment wasevaluated with an eye and judged as follows.

o: No deformation and no crinkling.

x: Deformed and many crinkles.

[Impact Resistance]

The container after sterilization treatment was cooled at 4° C. and fivecontainers held horizontally were dropped on a hard floor from a heightof 100 cm. The number of ruptured containers was counted.

[Transparency]

The container after sterilization treatment was measured on the lighttransmittance by using U-3300 manufactured by Hitachi Ltd. according toTransparency Test in Test Methods for Plastic Containers of The JapanesePharmacopoeia, 14th ed.

[Blocking Resistance]

The container after sterilization treatment was left standing at 23° C.for 24 hours and then inner surfaces were pulled apart. The degree ofpower necessary for the separation and the separated surface state wereobserved with an eye and judged as follows. o: Readily separated. x: Notseparated. TABLE 3 Film Impact Number Resistance Light of InnerIntermediate Outer Heat (number of Transmittance Blocking Layers LayerLayer Layer Resistance ruptured bags) (%) Resistance Example 1 1 —Composition 1 — ∘ 0 79 ∘ Example 2 1 — Composition 2 — ∘ 0 77 ∘ Example3 1 — Composition 3 — ∘ 0 80 ∘ Example 4 3 PE 1 Composition 3 PE 1 ∘ 079 ∘ Example 5 2 — Composition 8 PE 1 ∘ 0 74 ∘ Example 6 3 PE 1(70%) +Composition 6 PE 1 ∘ 0 76 ∘ PE2(30%) Example 7 3 PE 1 Composition 7 PE 1∘ 0 68 ∘ Example 8 3 PE 1 Composition 3 A11-2 ∘ 0 82 ∘ Example 9 3 A11-2 Composition 8 A11-2 ∘ 0 78 ∘ Comparative 1 — Composition 4 — ∘ 1 78∘ Example 1 Comparative 1 — Composition 5 — ∘ 0 45 ∘ Example 2Comparative 1 — Composition 9 — ∘ 5 46 ∘ Example 3 Comparative 3 PE 1Composition 5 PE 1 ∘ 0 51 ∘ Example 4 Comparative 3 PE 2 Composition 4PE 2 x 0 44 x Example 5

The medical containers of Examples 1 to 9 were produced from a filmcomprising a polyolefin resin composition containing (A) apropylene-base polymer and (B) an ethylene-base polymer and moreover,the xylene-soluble portion of the polyolefin resin composition had arefractive index of 1.480 to 1.495, therefore, these containers wereexcellent in the heat resistance, impact resistance, transparency andblocking resistance.

On the other hand, in the medical containers of Comparative Examples 1,2 and 4, the xylene-soluble portion of the polyolefin resin compositionhad a refractive index out of the range from 1.480 to 1.495 andtherefore, the transparency was low.

Furthermore, the medical container of Comparative Example 3 was producedfrom a film comprising a polyolefin resin composition of onlypropylene-base polymer (A) and moreover, the xylene-soluble portion ofthe polyolefin resin composition had a refractive index out of the rangefrom 1.480 to 1.495, therefore, the transparency and impact resistancewere low.

In the medical container of Comparative Example 5, the xylene-solubleportion of the polyolefin resin composition had a refractive index outof the range from 1.480 to 1.495 and therefore, the transparency waslow. Moreover, a layer comprising a linear low-density polyethylene wasprovided in the inner and outer sides, therefore, the heat resistanceand blocking resistance were insufficient.

INDUSTRIAL APPLICABILITY

The medical container of the present invention has heat resistance highenough to enable sterilization at a temperature of 121° C. or more andat the same time, exhibits excellent properties in all of thetransparency, impact resistance, flexibility and blocking resistance.

1. A medical container produced from a film or sheet having at least oneresin layer comprising a polyolefin resin composition, wherein saidpolyolefin resin composition comprises (A) at least one propylene-basepolymer selected from the group consisting of (A1) a propylene-basepolymer composition as a mixture of (A11) a propylene polymer and (A12)an ethylene-propylene copolymer elastomer, (A2) a propylene-base blockcopolymer, and (A3) a propylene-base block copolymer composition as amixture of (A2) a propylene-base block copolymer and (A12) anethylene-propylene copolymer elastomer, and (B) an ethylene-basecopolymer comprising an ethylene and at least one α-olefin having 4 ormore carbon atoms, and the refractive index of the xylene-solubleportion is from 1.480 to 1.495.
 2. The medical container as claimed inclaim 1, wherein said polyolefin resin composition has a xylene-solubleportion content of 20 to 70 mass %.
 3. The medical container as claimedin claim 1, wherein in said polyolefin resin composition, the ratio(MFR_(A)/MFR_(B)) of the melt flow rate (MFR_(A)) of propylene-basepolymer (A) to the melt flow rate (MFR_(B)) of ethylene-base copolymer(B) is from 0.3 to 3.0.
 4. The medical container as claimed in claim 1,wherein said film or sheet has a first high-density polyethylene layercomprising a high-density polyethylene and said first high-densitypolyethylene layer is disposed in the inner side.
 5. The medicalcontainer as claimed in claim 1, wherein said film or sheet has a secondhigh-density polyethylene layer comprising a high-density polyethyleneand said second high-density polyethylene layer is disposed in the outerside.
 6. The medical container as claimed in claim 4, wherein said firsthigh-density polyethylene layer contains 20 mass % or more of ahigh-density polyethylene having a density of 0.950 g/cm³ or more. 7.The medical container as claimed in claim 5, wherein said secondhigh-density polyethylene layer contains 20 mass % or more of ahigh-density polyethylene having a density of 0.950 g/cm³ or more. 8.The medical container as claimed in claim 1, wherein the thickness ofthe resin layer comprising a polyolefin resin composition occupies 60%or more of the entire thickness of the film or sheet.